P904: CILTACABTAGENE AUTOLEUCEL VS TREATMENTS FROM REAL-WORLD CLINICAL PRACTICE FOR TRIPLE CLASS EXPOSED PATIENTS WITH MULTIPLE MYELOMA: ADJUSTED COMPARISONS BASED ON CARTITUDE-1 AND THE EMMY FRENCH COHORT
Authors: O. Decaux, C. Hulin, A. Perrot, M. Macro, L. Frenzel, J. Diels, N. J. Perualila, F. Ghilotti, B. Haefliger, E. Goldsztajn, S. Vernet, J. Thevenon, M. Willaime, N. Texier, J. M. Schecter, D. Madduri, C. Jackson, S. Valluri, P. Moreau
Journal: HemaSphere (2022)

Background: The prognosis of patients with triple-class (TC) exposed, relapsed and refractory multiple myeloma (RRMM) is poor. CARTITUDE-1 is an open-label, single arm, phase 1b/2 clinical trial performed to assess the safety and efficacy of ciltacabtagene autoleucel (cilta-cel), a novel chimeric antigen receptor T-cell therapy. Adjusted comparisons to other therapies used in real-world clinical practice (RWCP) help inform the relative efficacy of cilta-cel in TC exposed patients. The Epidemiology of the therapeutic management of Multiple MYeloma in France (EMMY) study is a retrospective study capturing information on the therapeutic management of patients from 71 centers in France, and can serve as an external control arm for CARTITUDE-1. Aims: To compare cilta-cel with treatments from RWCP in terms of overall response rate (ORR), very good partial response or better rate (≥VGPR), progression-free survival (PFS), and overall survival (OS). Methods: Adjusted comparisons were estimated using individual patient data (IPD) from CARTITUDE-1 (cut-off date July 2021) and reconstructed IPD from EMMY (cut-off date March 2021). Within EMMY, all treatment lines initiated after a patient met eligibility criteria (TC exposed patients in L4+ and ECOG<2) were used for analysis, so long as eligibility remained intact. Inverse probability weighting (IPW) was used to balance the cilta-cel and RWCP groups on prognostic baseline variables including refractory status, time to progression on prior line of treatment (LOT), number of prior LOTs, ECOG performance status, age, sex, years since MM diagnosis, average duration of prior LOTs, MM type, and prior transplant. Weights derived from propensity scores estimated with a multivariable logistic regression and were assigned to EMMY patients, such that the weighted EMMY cohort reflected the CARTITUDE-1 population. Balance was assessed using standardized mean differences (SMD). The relative efficacy of cilta-cel versus RWCP was assessed using relative response rates (RR) for binary outcomes and hazard ratios (HR) for time-to-event outcomes, using weighted logistic regression and proportional hazards modeling, respectively. Main analyses were performed in the population of infused patients in the cilta-cel group and an aligned population of EMMY RWCP patients that included those still progression-free after 52 days (mean time between apheresis and cilta-cel infusion). Similar analyses were performed for all enrolled patients. Results: 113 patients were enrolled in CARTITUDE-1 and 97 received cilta-cel infusions. 437 LOTs (238 patients) from EMMY were included in the RWCP external control arm and 309 LOTs (227 patients) were alive and progression-free after 52 days. More than 100 treatment regimens within the RWCP group were used. After reweighting, baseline traits were balanced between groups, with all SMD <0.20. ORR (RR 5.1, 95% CI: 3.7;7.1) and ≥VGPR (RR 14.5 [8.0; 26.1] were superior with cilta-cel vs. RWCP, as were both PFS (HR 0.15 [0.10; 0.22]) and OS (HR 0.21 [0.12; 0.37]). Results for the enrolled populations were consistent (see Table). Image:Summary/Conclusion: Adjusted comparisons between cilta-cel and RWCP in France showed superior efficacy on all outcomes for cilta-cel vs. RWCP, with 5.1 and 14.5-fold higher response rates for ORR and ≥VGPR, respectively, and reduced risks of disease progression/death and death by 85% and 79% with cilta-cel versus RWCP. These findings align with results from similar comparisons in other countries. Cilta-cel offers substantial clinical benefits for patients with triple class exposed RRMM.